Hepatic ischemia-reperfusion injury(HIRI)is the cause of postoperative hepatic dysfunction and failure,and even death.As an important biological effector molecule,hydrogen sulfide(H_(2)S)of mitochondria as a gasotrans...Hepatic ischemia-reperfusion injury(HIRI)is the cause of postoperative hepatic dysfunction and failure,and even death.As an important biological effector molecule,hydrogen sulfide(H_(2)S)of mitochondria as a gasotransmitter that is usually used to protect against acute HIRI injury.However,the exact relationship between HIRI and mitochondrial H_(2)S remains tangled due to the lack of an effective analytical method.Herein,we have fabricated a mitochondria-targeted H_(2)S-activatable fluorogenic probe(Mito-GW)to explore the stability of mitochondrial H_(2)S and track the changes of mitochondrial H_(2)S during the HIRI.By virtue of pyridinium electropositivity and its amphiphilicity,Mito-GW could accumulate in mitochondria.It goes through an analyte-prompted immolation when reacts with H_(2)S,resulting in the releasing of the fluorophore(GW).Therefore,the extent of Mito-GW conversion to GW can be used to evaluate the changes of mitochondrial H_(2)S level in living cells and tissues.As proof-of-principle,we have used MitoGW to demonstrate the mitochondria H_(2)S-levels increase and then decrease during HIRI in vitro and in vivo.Our research highlights the tremendous potential of Mito-GW as a mitochondrial H_(2)S fluorogenic probe in elucidating the pathogenesis of HIRI,providing a powerful tool for promoting future research on hepatology.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.22077101,22004099)the Joint Research Funds of Department of Science&Technology of Shaanxi Province and Northwestern Polytechnical University(Nos.2020GXLH-Z-008,2020GXLH-Z-021,2020GXLH-Z-023)+4 种基金Natural Science Foundation of Shaanxi Province(No.2022JM-130)The Natural Science Foundation of Ningbo(Nos.202003N4049,202003N4065)the Open Project Program of Wuhan National Laboratory for Optoelectronics(Nos.2020WNLOKF023,2022WNLOKF009)Innovation Foundation for Doctor Dissertation of Northwestern Polytechnical University(No.CX2022034)Innovation Capability Support Program of Shaanxi(No.2023-CX-PT-23)。
文摘Hepatic ischemia-reperfusion injury(HIRI)is the cause of postoperative hepatic dysfunction and failure,and even death.As an important biological effector molecule,hydrogen sulfide(H_(2)S)of mitochondria as a gasotransmitter that is usually used to protect against acute HIRI injury.However,the exact relationship between HIRI and mitochondrial H_(2)S remains tangled due to the lack of an effective analytical method.Herein,we have fabricated a mitochondria-targeted H_(2)S-activatable fluorogenic probe(Mito-GW)to explore the stability of mitochondrial H_(2)S and track the changes of mitochondrial H_(2)S during the HIRI.By virtue of pyridinium electropositivity and its amphiphilicity,Mito-GW could accumulate in mitochondria.It goes through an analyte-prompted immolation when reacts with H_(2)S,resulting in the releasing of the fluorophore(GW).Therefore,the extent of Mito-GW conversion to GW can be used to evaluate the changes of mitochondrial H_(2)S level in living cells and tissues.As proof-of-principle,we have used MitoGW to demonstrate the mitochondria H_(2)S-levels increase and then decrease during HIRI in vitro and in vivo.Our research highlights the tremendous potential of Mito-GW as a mitochondrial H_(2)S fluorogenic probe in elucidating the pathogenesis of HIRI,providing a powerful tool for promoting future research on hepatology.
